Seeinstructions): This HIVRAD program builds upon our recent successes in generating stable, proteolytically mature gp140 trimers (SOSIP gp140s) that mimic virion-associated envelope (Env) in topology and antigenicity. The overall goals of this HIVRAD program are reflected in three major milestones: 1) determine the structure of cleaved Env trimers at <4A resolution, 2) demonstrate methods to overcome HIV-1 Env's immunosuppressive properties, and 3) identify a SOSIP trimer vaccine that elicits heterologous neutralization of diverse HIV-1 isolates. Core A will be responsible for the overall scientific leadership of the HIVRAD. In addition, Core A will coordinate the highly inter-dependent and interactive studies to be performed in Project 1 (HIV-1 Env Vaccine Design, Dr. Moore) and Project 2 (HIV-1 Env Trimer Crystallography, Dr. Wilson) with technical support from Core B (Trimer Production and Immunogenicity Testing, Dr. Olson). Core A will provide a broad range of management support necessary to meet the goals of the HIVRAD program. The key functions of Core A can be grouped according to three Specific Aims: 1) Provide overall scientific direction and coordination for the program;2) Facilitate sharing of research data and resources within the program and with the broader scientific community;and 3) Provide statistical, fiscal, administrative and intellectual property support. These Aims will be accomplished by an existing team of professionals with significant industry experience in each of the functional areas. The Core activities are central to the overall success of the HIVRAD program. Core A will facilitate the timely exchange of materials, data and other information between Project 1, Project 2 and additional collaborators. The interactive nature of the program necessitates that information and materials generated in the program be exchanged in a timely fashion with the participating members of the HIVRAD, and Core A will responsible for ensuring timely interactions between the HIVRAD Projects and Cores in order to optimally advance the program. In addition, Core A will establish and annually convene an external Scientific Advisory Group to assist with decisions on the direction of the research program. The overall role of Core A is to optimally coordinate, direct and facilitate the research of Project 1 and Project 2 in order to achieve our shared goal of providing a fundamental advance towards an HIV-1 vaccine. RELEVANCE (Seeinstructions): Nearly 1% of the world's population is infected with HIV, and a preventive vaccine is urgently needed. Most efficacious vaccines elicit antibodies that can neutralize the pathogen, but current-generation HIV vaccines are not effective in this regard. Obstacles include our limited understanding of the structure and immunology of HIV-1 envelope trimers. This HIVRAD represents an innovative approach to addressing these challenges in order to provide a fundamental advance in our ability to elicit HIV-neutralizing antibodies with a vaccine.